Herein we develop a unique differentiated-uptake strategy capable of efficient and high-purity isolation of genuine drug-resistant (DR) cells from three types of drug-surviving cancer cells, which include paclitaxel-surviving human ovarian OVCAR-3 cancer cells and human lung carcinoma A549/Taxol cells, and doxorubicin-surviving human immortalized myelogenous leukemia K562/ADR cells. By using this strategy which relies on fluorescent glycan nanoparticle (FGNP)-based fluorescence-activated cell sorting (FACS) assays, two subpopulations with distinct fluorescences existing in drug-surviving OVCAR-3 cells were separated, and we found that the lower fluorescence (LF) subpopulation consisted of DR cells, while the higher fluorescence (HF) subpopulation was comprised of non-DR cells. Besides, the DR cells and their progenies were found distinct in their increased expression of drug-resistant genes. More intriguingly, by using the FGNP-based FACS assay to detect DR/non-DR phenotypes, we found that the DR phenotype had a potential to differentiate into the non-DR progeny, which demonstrates the differentiation feature of stem-like cancer cells. Further research disclosed that the assay can quantitatively detect the degree of drug resistance in DR cells, as well as the reversal of drug resistance that are tackled by various therapeutic methods. The strategy thus paves the way to develop theranostic approaches associated with chemotherapy-resistance and cancer stemness.

中文翻译：

---

基于荧光聚糖纳米颗粒的FACS测定法鉴定具有分化潜能的真正耐药癌细胞

本文中，我们开发了一种独特的差异吸收策略，能够从三种类型的存活药物的癌细胞中高效，高纯度地分离出真正的耐药（DR）细胞，其中包括存活紫杉醇的人卵巢OVCAR-3癌细胞和人类肺癌A549 / Taxol细胞和存活阿霉素的人类永生化骨髓性白血病K562 / ADR细胞。通过使用这种基于荧光聚糖纳米（FGNP）的荧光激活细胞分选（FACS）分析的策略，可以分离出两个存活于药物存活的OVCAR-3细胞中的具有不同荧光的亚群，我们发现较低的荧光（ LF）亚群由DR细胞组成，而较高的荧光（HF）亚群则由非DR细胞组成。除了，发现DR细胞及其后代的不同之处在于其耐药基因的表达增加。更有趣的是，通过使用基于FGNP的FACS检测来检测DR /非DR表型，我们发现DR表型具有分化为非DR后代的潜力，这证明了干细胞样癌细胞的分化特征。进一步的研究表明，该测定法可以定量检测DR细胞中的耐药性程度以及通过各种治疗方法解决的耐药性逆转。因此，该策略为开发与化疗耐药性和癌症干性相关的诊断方法铺平了道路。我们发现DR表型具有分化为非DR后代的潜力，这证明了干细胞样癌细胞的分化特征。进一步的研究表明，该测定法可以定量检测DR细胞中的耐药性程度以及通过各种治疗方法解决的耐药性逆转。因此，该策略为开发与化疗耐药性和癌症干性相关的诊断方法铺平了道路。我们发现DR表型具有分化为非DR后代的潜力，这证明了干细胞样癌细胞的分化特征。进一步的研究表明，该测定法可以定量检测DR细胞中的耐药性程度以及通过各种治疗方法解决的耐药性逆转。因此，该策略为开发与化疗耐药性和癌症干性相关的诊断方法铺平了道路。